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Lymphovascular Invasion Predicts Cancer-Specific Mortality in Penile Localized Squamous Cell Carcinoma - Beyond the Abstract

Penile squamous cell carcinoma (SCCP) is a rare yet aggressive malignancy, with survival outcomes that vary considerably, especially in patients with localized disease. While lymphovascular invasion (LVI) has long been recognized as an adverse prognostic marker in several genitourinary cancers, its role in predicting cancer-specific mortality (CSM) in localized SCCP remained unclear prior to our study.

In our analysis of 685 patients with T1b-T2N0M0 SCCP from the SEER database (2010–2021), we demonstrated that LVI is a powerful independent predictor of CSM. Specifically, patients with LVI-positive tumors had significantly worse CSM-free survival at three years compared to their LVI-negative counterparts (69% vs. 85%), with an adjusted hazard ratio of 2.6. Importantly, this prognostic effect was consistent across both T1b and T2 substages, indicating a robust association.

These findings carry relevant implications for clinical decision-making. In patients with localized SCCP, LVI status may help stratify the risk of disease-specific mortality, potentially informing the intensity of follow-up, the decision to perform early lymphadenectomy, or the consideration of adjuvant therapies, even in the absence of nodal involvement.

Unlike previous studies, which often examined broader stage groups or used overall survival (OS) as the primary endpoint, our study focused on cancer-specific outcomes in a truly localized cohort. This distinction is crucial because OS in localized SCCP is often confounded by other-cause mortality. By focusing on CSM, we highlight the specific risk attributable to cancer biology rather than competing causes of death.

Despite inherent limitations related to the retrospective design and the absence of variables such as HPV status or margin data, our findings support incorporating LVI into routine prognostic assessment for localized SCCP. Future prospective studies should aim to validate these findings and assess whether intensified management strategies for LVI-positive patients translate into improved outcomes.

Written by: Natali Rodriguez Peñaranda,1 Letizia Maria Ippolita Jannello,2 Francesco Di Bello,3 Carolin Siech,4 Mario de Angelis,5 Jordan A. Goyal,6 Zhe Tian,6 Fred Saad,6 Shahrokh F. Shariat,7 Nicola Longo,8 Felix K. H. Chun,9 Alberto Briganti,10 Ottavio de Cobelli,11 Stefano Di Bari,12 Stefano Puliatti,12 Salvatore Micali,12 Pierre I. Karakiewicz6

  1. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology, AOU di Modena, University of Modena and Reggio Emilia, Modena, Italy.
  2. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Urology, IEO European Institute of Oncology, IRCCS, Milan, Italy; Università degli Studi di Milano, Milan, Italy.
  3. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, Naples, Italy.
  4. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Goethe University Frankfurt, University Hospital, Department of Urology, Frankfurt am Main, Germany.
  5. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada; Vita-Salute San Raffaele University, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
  6. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.
  7. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.
  8. Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, Naples, Italy.
  9. Goethe University Frankfurt, University Hospital, Department of Urology, Frankfurt am Main, Germany.
  10. Vita-Salute San Raffaele University, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
  11. Department of Urology, AOU di Modena, University of Modena and Reggio Emilia, Modena, Italy; Università degli Studi di Milano, Milan, Italy; Department of Oncology and Haemato-Oncology, Università degli Studi di Milano, Milan, Italy.
  12. Department of Urology, AOU di Modena, University of Modena and Reggio Emilia, Modena, Italy.
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